Women take a lot of criticism for premenstrual syndrome, being accused by male friends and partners of irritability and moodiness. Now, women may have a good explanation for their behavior.

During the 2 weeks before their period, women experience a gradual surge of progesterone secretion. Progesterone is produced by an ovulated egg within the ovaries, and is released into the bloodstream. Is has effects throughout the body, most recognizably in preparing the lining of the uterus for implantation of a fertilized egg.

Progesterone is metabolized into several different compounds. Two of these metabolites, allopregnenolone and pregnenolone, are capable of crossing the blood-brain barrier and affecting neural function. Previous research showed these two molecules to increase the activity of the neurotransmitter GABA, which has effects throughout the cerebral cortex. Animal studies demonstrated increased anxiety with administration of progesterone, suggesting that it affects parts of the brain related to anxiety and mood.

In order to investigate the effect of progesterone in humans, researchers recruited females and monitored brain activity following progesterone administration. The women were given progesterone during the follicular phase of their menstrual cycle, the phase just before a physiological increase in progesterone occurs each month. The dose increased their serum progesterone and allopregnenolone levels to the normal values seen during premenstrual and early pregnancy periods. Functional magnetic imaging (fMRI) of the participants brains found increased brain activity localized to the amygdala, a small region deep within the brain that is responsible for emotions and emotional memory. This new data provides a link between the physiological progesterone surge seen just before menstruation and mood changes that occur at this same time. This information may be applicable to providing treatment for women who suffer from severe PMS — or least providing a biological explanation for womenâ€™s seemingly irrational behavior!

Lindsey Kay, MD, is a medical doctor with training in pathology, and an avid writer. During his training, he worked on pre-clinical and clinical trials in a variety of laboratories related to alcohol effects on the brain, cancer diagnosis, and alternative medicine.

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